Introduction

Recent years have seen the sequencing of the complete genome of human and major model organisms, opening – and demanding – new discovery paradigms. By using a combination of high-throughput methodologies and sophisticated information analysis, several new approaches promise to add function to the raw “sequence” blueprint of life. Currently, high-throughput technologies have been applied to study the transcriptome, by expression profiling (Brown and Botstein, 1999) and ChIP on chip (Wyrick and Young, 2002), the proteome (2D gel-electrophoresis and mass-spectrometry analysis) and protein–protein interactions [(two-hybrid screens, affinity-tag purification coupled with mass-spectrometry, protein chips) (Uetz et al., 2000; Gavin et al., 2002; Drewes and Bouwmeester, 2003; Giot et al., 2003; Li et al., 2004)]. Genome-wide reverse genetic approaches have recently entered the field. In yeast, deletion strains for every gene transcript have been constructed and allow the functional analysis on a genome-wide scale (Wagner et al., 1997; Giaever et al., 2002). Similarly, genome-wide RNAi experiments promise to deliver functional information both in whole-animal assays and focused cell-based screening applications. Typically, hypothesis-driven experiments have relied on combining the strength of different experimental approaches to infer statements about functional properties. It can be similarly expected that in the medium term, a combination of multiple “data-rich” genomic technologies will be required to formulate and test hypotheses about system properties. Ultimately, this should enable us to accurately change physiological systems to prevent or cure disease conditions.

Genome-wide functional screens have become one of the key next challenges to systematically discover gene function.